Shetty 2015.

Study characteristics
Patient Sampling	Retrospective single‐centre case‐control study in people with clinically diagnosed keratoconus before they received corneal crosslinking (85 eyes) and normal controls before they received an ablation (43 eyes).
Patient characteristics and setting	The diagnosis of keratoconus was based on evidence of stromal thinning, focal protrusion, or increase in corneal curvature, Fleischer's ring, Vogt's striae, scissoring of the red reflex, an abnormal retinoscopy, and curvature asymmetry leading to abnormal corneal astigmatism. For normal eyes, manifest spherical error and astigmatism were limited to ±2 D. Exclusion criteria were ocular hypertension, corneal inflammation, prior eye surgery, and current topical medication use.
Index tests	Logistic regression using Zernike coefficients, curvature, corneal volume, and corneal anterior wavefront analyses to calculate if keratoconus is present.
Target condition and reference standard(s)	The diagnosis of keratoconus was based on evidence of stromal thinning, curvature asymmetry leading to abnormal corneal astigmatism, or increase in corneal curvature measured by the Pentacam, and clinical signs (e.g. Fleischer ring's, Vogt's striae, scissoring of the red reflex, an abnormal retinoscopy, and focal protrusion). However, it was unclear who made the diagnosis.
Flow and timing	It was unclear whether all participants received the same reference standard. All participants were included in the analysis.
Comparative	Multiple logistic regression equations were compared; however, it was unclear if the development and interpretation was done without the knowledge of each other and if all cases were analysed by all the equations.
Notes	Dr Dupps is a recipient of National Eye Institute, USA R01 grant (# NIH R01 EY023381).
Methodological quality
Item	Authors' judgement	Risk of bias	Applicability concerns
DOMAIN 1: Patient selection
Was a consecutive or random sample of patients enrolled?	No
Was a case‐control design avoided?	No
Did the study avoid inappropriate exclusions?	Yes
Could the selection of patients have introduced bias?		High risk
Are there concerns that the included patients and setting do not match the review question?			High
DOMAIN 2: Index test (All tests)
Were the index test results interpreted without knowledge of the results of the reference standard?	Yes
If a threshold was used, was it pre‐specified?	Unclear
Was the model designed in an appropriate manner?	Yes
Could the conduct or interpretation of the index test have introduced bias?		Low risk
Are there concerns that the index test, its conduct, or interpretation differ from the review question?			Low concern
DOMAIN 3: Reference standard
Is the reference standard likely to correctly classify the target condition?	Unclear
Were the reference standard results interpreted without knowledge of the results of the index tests?	No
Could the reference standard, its conduct, or its interpretation have introduced bias?		Unclear risk
Are there concerns that the target condition as defined by the reference standard does not match the question?			Unclear
DOMAIN 4: Flow and timing
Did all patients receive the same reference standard?	Unclear
Were all patients included in the analysis?	Yes
Could the patient flow have introduced bias?		Unclear risk
DOMAIN 5: Comparative
Were different AI tests were developed and interpreted without knowledge of each other.	Unclear
Are the proportions and reasons for missing data similar for all index tests?	Unclear
		Unclear risk